Agomelatine hydrochloride (S-20098 hydrochloride) is a specific MT1 and MT2 receptor agonist with Ki values of 0.1 nM for CHO-hMT1, 0.06 nM for HEK-hMT1, 0.12 nM for CHO-hMT2, and 0.27 nM for HEK-hMT2, respectively [1]. Additionally, Agomelatine hydrochloride is a selective antagonist of the 5-HT2C receptor with pKi values of 6.4 and 6.2 for native (porcine) and cloned human 5-HT2C receptors, respectively [2].

MT2 (human):0.12 (Ki, CHO Cells), MT1 (human):0.1 (Ki, CHO Cells), MT2 (human):0.27 (Ki, HEK Cells), 5-HT2C receptor:6.4 (pKi, native porcine), MT1 (human):0.06 (Ki, HEK Cells), 5-HT2C receptor:6.2 (pKi, human)

Agomelatine (S 20098) functions as a full agonist for the MT1 and MT2 receptors, exhibiting EC50 values of 1.6±0.4 and 0.10±0.04 nM, respectively, when expressed in CHO or HEK cell membranes. Additionally, Agomelatine interacts with h5-HT2B receptors, displaying a marked preference (6.6). However, it demonstrates low affinity for both native and cloned human 5-HT2A receptors, with values just below 5.0/5.3, and similarly low affinity for 5-HT1A receptors (below 5.0/5.2), while exhibiting negligible affinity for other 5-HT receptors.

Agomelatine (25, 50, or 75 mg/kg; i.p.) exhibits antioxidant activity in Strychnine (75 mg/kg, i.p.) or Pilocarpine (400 mg/kg, i.p.) induced seizure models in mice, but does not affect oxidative stress parameters in Pentylenetetrazole (PTZ) or Picrotoxin (PTX) induced seizure models compared to controls[3].